Amino compounds represented by the following general formula (I): ##STR2## wherein R.sup.1 and R.sup.2 independently represent hydrogen atom or a lower alkoxy group, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 independently represent hydrogen atom, amino group or a lower alkoxy group with at least one of R.sup.3 -R.sup.6 being amino group, and R.sup.7 is a lower alkyl group, which are useful for pharmaceutical use, particularly for the treatment of liver or allergic diseases, have two epimers, that is, 1RS-3'RS epimer (hereinafter referred to as A-mer) and 1RS-3'SR epimer (hereinafter referred to as B-mer). They are utilized independently or in a mixture thereof, depending on purpose. It is generally necessary, therefore, to isolate one epimer, for example A-mer, from a reaction mixture for their preparation, when they are to be used singly in the form of A-mer only.
Generally, such amino compounds of the general formula (I) are prepared by reducing nitro compounds represented by the following general formula (II): ##STR3## wherein R.sup.1, R.sup.2 and R.sup.7 are as defined above, and R.sup.3', R.sup.4', R.sup.5' and R.sup.6' independently represent hydrogen atom, nitro group or a lower alkoxy group with at least one of R.sup.3' -R.sup.6' being nitro group. The nitro compounds of the general formula (II) may be prepared by condensation of tetrahydroisoquinolines represented by the following general formula (III): ##STR4## wherein R.sup.1, R.sup.2 and R.sup.7 are as defined above, with nitrophthalides represented by the following general formula (IV): ##STR5## wherein R.sup.3' -R.sup.6' are as defined above.
In the condensation reaction of the tetrahydroisoquinolines and the nitrophthalides, the nitro compounds of the general formula (II) are obtained in the form of a mixture of A-mer and B-mer. When the mixture is then reduced, the resulting amino compounds of the general formula (I) are obtained, of course, in the form of a mixture of A-mer and B-mer. Therefore, it is desirable to increase the yield of A-mer by preventing the formation of B-mer in the condensation procedure, when only A-mer is required.
In order to efficiently obtain A-mer of the amino compounds of the general formula (I), there has been proposed a method which comprises epimerization of B-mer into A-mer of the nitro compounds of the general formula (II) by a certain treatment of the mixture obtained by the condensation of the tetrahydroisoquinolines of the general formula (III) and the nitrophthalides of the general formula (IV).
In such a method, however, the nitro compounds may be partly decomposed in the epimerization process, although the epimerization of B-mer into A-mer may be certainly performed well. In addition to such a defect, there is a problem of safety due to the nitro group in the molecule when B-mer is to be recycled to the epimerization process after separation of A-mer from the epimerized mixture.
It has generally been considered that such an epimerization may proceed in a compound having an electron attracting group such as nitro group in the phthalide ring and, on the other hand, a compound having an electron donating group such as amino group is not well processed in such an epimerizaton process. This is the reason why the epimerization has been carried out on the nitro compounds of the general formula (II), not on the amino compounds of the general formula (I), in such a method as above-described even though there are some demerits mentioned above.
In consideration of such circumstances, the present inventors have made great efforts on the study of a process for efficient preparation of A-mer of the amino compounds represented by the formula (I) and finally found that, when treated under special conditions, such amino compounds which have been considered to be difficulty epimerized can be in fact processed, so that the B-mer can well be converted into the A-mer without any significant decomposition of the amino compounds.